Ger Brophy, PhDExecutive Vice PresidentBiopharma ProductionAvantor

Genuine progress is being made in the longstanding battle to effectively treat and control cancer. The National Cancer Institute projects that nearly five million more U.S. citizens are expected to survive cancer in 2029 than in 2019.1 Therapeutic tools such as next-generation sequencing and advances in immunotherapy are just two ways that fundamental scientific breakthroughs and innovative thinking are realizing the potential for new cancer treatments.

One of the most revolutionary breakthroughs in this new era is cell and gene therapy. At its most basic definition, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patients cells as a drug to treat disease. According to a paper published in the Journal of Gene Medicine, somewhere around 2600 gene therapy clinical trials had been undertaken in 38 countries around the world as of November 2017.2

These clinical trials demonstrate that the recent attention being paid to gene and cell therapy is not just hype. Some have noted that a select number of approved cell and gene therapies are for relatively small patient groups. However, its exciting to see the number of trials grow, especially when one considers this technologys ability to impact patients lives.

Its true that the number of patients receiving treatment is relatively small compared to other therapeutic regimens, but thats to be expected. Many of the biopharmaceutical researchers and manufacturers started with smaller, defined patient populations and, in particular, those with pediatric relapse refractory acute lymphoblastic leukemia. In part, these early efforts were directed at this type of cancer because the researchers wanted to deal with small populations that they understood well and, in many cases, had few or no other options for treatments.

The success of these initial efforts has led to broader programs targeting larger populationsstarting with leukemia and lymphoma. Ultimately, the most challenging opportunityand the one with the greatest potential for beneficial outcomesis multiple myeloma. If these patients begin to see benefits from cell and gene therapies, it will justify the incremental approach the industry has been taking.

The genuine, almost unprecedented potential for cell and gene therapy cannot be understated. For the first time, people are talking about curing these ruthless, relentless diseases. In a way never before possible, were taking control of and harnessing the patients own immune system to fight these cancers. Among the first patients treated for acute lymphoblastic leukemia, several are alive and thrivingfour, five, and six years later.

The game changer here is that cell and gene therapy uses the bodys own systems, either the cellular immune system or the ability to repair and replace defective or missing genes. CAR T-cell therapy is arguably among the most personalized medicines one can consider. The patients own T cells are extracted, modified, activated, expanded, purified, and returned to the patient.

Significant growth is underway in the size and sophistication of companies and organizations entering the cell and gene therapy markets. Many of the early movers in cell and gene therapy were small biotech startups. In some cases, their treatments were supported by major hospital centers.

Increasingly, weve all seen a greater interest from the major biopharma companies. Novartis was probably the biggest; it started earliest and was successful in getting approval for Kymriah. Since last year, weve seen several important acquisitions by Gilead and Bristol-Myers Squibb, and major biopharma companies are participating in large strategic partnerships in China. As companies of this size get involved, the hope is that they will leverage their increased breadth and depth to develop novel products, instigate new trials, and find ways to manufacture therapies at scale.

If the cell and gene therapy industry is to succeed, it must overcome challenges of two kinds: scalability and manufacturability. These challenges may be summarized in a set of questions: Can we manufacture cell and gene therapies at scale? If we can manufacture these treatments at scale, then can we do so safely? Can we do so at a reasonable cost so the populations that are affected by these diseases can access treatments?

With cell therapy, the single biggest point of variability is the patients own cells. By their very nature, these cells are individual to the patient, and their health implications for the patient should be considered as an integral part of cell processingat least as far back as the time of leukapheresis.

Variables and failure modes must be taken out of cell processing systems. We can standardize and miniaturize these systems, and we can enclose them so that theyre not exposed to failure modes. Also, we can improve technologies, like sterile fluid transfer, if we use excipient technology to further stabilize production. Finally, we can use analytical technology to understand the factors that contribute to a therapys success or failure.

Cell therapy producers and the companies that support and supply them need to become more innovative. In areas such as cell culture components, production chemicals, single-use technologies, sterile fluid transfer, and excipientsand the technology surrounding those process componentsthere is value to improving collaboration and trying new solutions to address the issues of manufacturability and scale.

We need to better analyze and understand the variability that comes from the research data, even at the early stages of these trials, and use it to correlate with clinical and process outcomes. Taking out manual steps as early as possible is important, as well as creating closed systems using sterile fluid transfer technologies.

One of the most significant challenges is finding solutions around side effects. As we understand how to provide a more efficacious dose, perhaps using fewer cells, some of the side effects of these drug therapies may improve. Furthermore, we must find scalable ways to reduce costs.

Ultimately, these drugs must be developed in a more cost-effective manner. Thats an area where technology providers and suppliers can play a significant role, by closing and automating systems and by understanding the contribution of labor and overhead and possible economies of scale from reducing processes.

There have been encouraging improvements in the way various regulatory groups have supported gene and cell therapy. To a certain degree, groups representing different regionsNorth America, Europe, and Asiahad been perceived to be setting precedents independently. More recently, it appears that regulatory bodies have been very open and collaborative in acknowledging that cell and gene therapies differ from more mature treatments such as biopharma drugs for cancer. The regulatory bodies have shown that they are willing to put the appropriate regulatory system into place to streamline the approval process and institute the ongoing monitoring of cell and gene therapies.

The U.S. FDAs support on CAR T-cell technologies is a good example. Regulators are allowing flexibility in the normal hierarchy of how clinical trials are performed, particularly in Phase II and III trials, but the companies must still address the FDAs postmarketing comments and safety issues.

Some have suggested that, ultimately, almost all cancer treatments will be based on gene and cell therapy approaches since they represent the most personalized form of treatment, which is, theoretically, the one with the highest potential for success.

Thats probably overly ambitious. Both large molecules and small molecules will continue to provide trusted, effective solutions with each type of drug product finding its niche. For example, large molecules are being developed for areas like neurodegeneration and are still offering great potential.

Its worth remembering that monoclonal-based therapies and biopharmaceuticals have really only started to make a significant impact in the last 15 to 20 years. Cell and gene therapies are just starting and have yet to make a significant market impact. But considerable effort is going into developing, understanding, and characterizing drug targets, as well as the development of technology to make targeted drugs in production-level volumes.

All these developments are exciting and offer a great deal of hope. It is clear that gene and cell therapies work and save lives. The challenge now is to scale their production. It is also clear that cell and gene therapies can emulate other therapeutic approaches that have transitioned from theoretical possibility to practical reality. As a similar transition occurs for cell and gene therapies, the production issues that need to be addressed will be seen more clearly, prompting action that will bring us to the next stage of development.

References1. Bluethmann SM, Mariotto AB, Rowland, JH. Anticipating the Silver Tsunami: Prevalence Trajectories and Comorbidity Burden among Older Cancer Survivors in the United States. Cancer Epidemiol. Biomarkers Prev. 2016; 25: 10291036.2. Ginn SL, Amaya AK, Alexander IE, et al. Gene therapy clinical trials worldwide to 2017: An update. J. Gene Med. 2018; 20(5): e3015.

Ger Brophy, PhD, is Executive Vice President, Biopharma Production at Avantor

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Opportunities and Challenges in Cell and Gene Therapy Development - Genetic Engineering & Biotechnology News

Healthcare is an industry that is currently being transformed using the latest technology, so it can meet the challenges it is facing in the 21st century. Technology can help healthcare organizations meet growing demand and efficiently operate to deliver better patient care. Here are 9 technology trends that will transform medicine and healthcare in 2020.

The 9 Biggest Technology Trends That Will Transform Medicine And Healthcare In 2020

AI and Machine Learning

As the world population continues to grow, and age, artificial intelligence, and machine learning offer new and better ways to identify disease, diagnose conditions, crowdsource and develop treatment plans, monitor health epidemics, create efficiencies in medical research and clinical trials, and make operations more efficient to handle the increased demands on the healthcare system. By 2020, medical data will double every 73 days. McKinsey estimates that there could be $100 billion in annual savings for medicine and pharma by leaning on big data as well as the artificial intelligence and machine learning tools to process it. Artificial intelligence algorithms powered by recent advances in computational power learn from the data and can predict the probability of a condition to help doctors provide a diagnosis and treatment plans. Ultimately, AI and machine learning can assist with many clinical problems as long as governing and regulatory bodies can determine how to regulate the use of algorithms in healthcare.

Robotics

When it comes to life or death, would you trust a robot with yours? Currently, collaborative robotssuch as the da Vinci surgical robot are already assisting humans with tasks in the operating room. However, the potential for robots in healthcare expands beyond surgical uses. With tremendous growth expected in the industrythe global medical robotics market is expected to reach $20 billion by 2023theres no doubt that robots used in healthcare will continue to conduct more varied tasks. These already include helping doctors examine and treat patients in rural areas via telepresence," transporting medical supplies, disinfecting hospital rooms, helping patients with rehabilitation or with prosthetics, and automating labs and packaging medical devices. Other medical robots that are promising include a micro-bot that can target therapy to a specific part of the body, such as radiation to a tumor or clear bacterial infections.

Computer and Machine Vision

Training computers to "see" the world and understand visual input is no small feat. Since there has been significant progress in machine vision, there are more ways computers and machine vision are being used in medicine for diagnostics, viewing scans and medical images, surgery, and more. Machine vision is helping doctors definitively know how much blood a woman loses in childbirth so that appropriate care can be given to reduce the mortality of mothers from post-partum hemorrhaging. Computers provide accurate intel, while previously this was a guessing game. The applications where computers are being used to view CT scans to detect neurological and cardiovascular illnesses and spot tumors in X-ray images are growing rapidly.

Wearable Tech

Wearable fitness technology can do much more than tell you how many steps you walk each day. With more than 80% of people willing to wear wearable tech, there are tremendous opportunities to use these devices for healthcare. Today's smartwatches can not only track your steps but can monitor your heart rhythms. Other forms of wearable devices are ECG monitors that can detect atrial fibrillation and send reports to your doctor, blood pressure monitors, self-adhesive biosensor patches that track your temperature, heart rate, and more. Wearable tech will help consumers proactively get health support if there are anomalies in their trackers.

Genomics

Artificial intelligence and machine learning help advance genomic medicinewhen a person's genomic info is used to determine personalized treatment plans and clinical care. In pharmacology, oncology, infectious diseases, and more, genomic medicine is making an impact. Computers make the analysis of genes and gene mutations that cause medical conditions much quicker. This helps the medical community better understand how diseases occur, but also how to treat the condition or even eradicate it. There are many research projects in place covering such medical conditions as organ transplant rejection, cystic fibrosis, and cancers to determine how best to treat these conditions through personalized medicine.

3D Printing

Just as it's done for other industries, 3D printing enabled prototyping, customization, research, and manufacturing for healthcare. Surgeons can replicate patient-specific organs with 3D printing to help prepare for procedures, and many medical devices and surgical tools can be 3D printed. 3D printing makes it easier to cost-effectively develop comfortable prosthetic limbs for patients and print tissues and organs for transplant. Also, 3D printing is used in dentistry and orthodontics.

Extended Reality (Virtual, Augmented and Mixed Reality)

Extended reality is not just for entertainment; its being used for important purposes in healthcare. The VR/AR healthcare market should reach $5.1 billion by 2025. Not only is this technology extremely beneficial for training and surgery simulation, but it's also playing an important part in patient care and treatment. Virtual reality has helped patients with visual impairment, depression, cancer, and autism. Augmented reality helps provide another layer of support for healthcare practitioners and aided physicians during brain surgery and reconnecting blood vessels. In mixed reality, the virtual and real worlds are intertwined, so it provides important education capabilities for medical professionals as well as to help patients understand their conditions or treatment plans.

Digital Twins

A digital twin is a near real-time replica of something in the physical worldin healthcare, that replica is the life-long data record of an individual. Digital twins can assist a doctor in determining the possibilities for a successful outcome of a procedure, help make therapy decisions, and manage chronic diseases. Ultimately, digital twins can help improve patient experience through effective, patient-centric care. The use of digital twins in healthcare is still in its early stages, but its potential is extraordinary.

5G

As the capabilities for healthcare centers to provide care in remote or under-served areas through telemedicine increase, the quality and speed of the network are imperative for positive outcomes. 5G can better support healthcare organizations by enabling the transmission of large imaging files so specialists can review and advise on care; allow for the use of AI and Internet of Things technology; enhance a doctor's ability to deliver treatments through AR, VR and mixed reality; and allow for remote and reliable monitoring of patients.

These technologies offer incredible opportunities to provide better healthcare to billions of people and make help our healthcare systems cope with the ever-increasing demands.

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The 9 Biggest Technology Trends That Will Transform Medicine And Healthcare In 2020 - Forbes

The Food and Drug Administration has halted a clinical trial of Novartis Zolgensma gene therapy due to a safety concern found in an animal study, the company said Wednesday.

The hold affects the Novartis (NVS) clinical trial known as STRONG, which was testing a higher dose of Zolgensma administered by spinal injection to older children with spinal muscular atrophy (SMA). It does not affect the already approved treatment of infants and children.

Novartis said its subsidiary AveXis informed regulators about findings from an animal study that showed dorsal root ganglia (DRG) mononuclear cell inflammation, sometimes accompanied by neuronal cell body degeneration or loss. The clinical significance of this adverse safety signal is not known, but it can be associated with sensory effects, the company added.

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Halting the STRONG clinical trial is a setback for Novartis effort to expand the use of Zolgensma to older patients with SMA. Biogens Spinraza treatment is already approved for older SMA patients. Roche (RHHBY) is expected to secure approval of its own SMA treatment next year.

Novartis said it has seen no reports of sensory effects in patients and is working with the FDA to resolve safety concerns and resume dosing of Zolgensma in the clinical trial.

The FDAs action on Wednesday follows a controversy involving manipulation of data used to support Zolgensmas approval. In an unusual rebuke, the agency said in August that AveXis knew that preclinical data had been falsified before the drug was approved in May, but did not inform the agency until later. The agency said that the drug should stay on the market, but the scandal sparked anger from lawmakers and a pledge from Novartiss CEO, Vas Narasimhan, to move more quickly on disclosing issues around data integrity.

Zolgensma carries a price tag of $2.1 million, making it the worlds most expensive medicine. Earlier this month, Novartis said the gene therapy had been used to treat 100 patients since its launch and brought in $160 million in the third quarter, beating analysts expectations.

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Novartis' Zolgensma gene therapy study halted on animal safety concerns - STAT

The story so far: The Council of Scientific and Industrial Research (CSIR) recently announced the conclusion of a six-month exercise (from April 2019) of conducting a whole-genome sequence of a 1,008 Indians. The project is part of a programme called IndiGen and is also seen as a precursor to a much larger exercise involving other government departments to map a larger swathe of the population in the country. Project proponents say this will widen public understanding in India about genomes and the information that genes hide about ones susceptibility to disease.

A genome is the DNA, or sequence of genes, in a cell. Most of the DNA is in the nucleus and intricately coiled into a structure called the chromosome. The rest is in the mitochondria, the cells powerhouse. Every human cell contains a pair of chromosomes, each of which has three billion base pairs or one of four molecules that pair in precise ways. The order of base pairs and varying lengths of these sequences constitute the genes, which are responsible for making amino acids, proteins and, thereby, everything that is necessary for the body to function. It is when these genes are altered or mutated that proteins sometimes do not function as intended, leading to disease.

Sequencing a genome means deciphering the exact order of base pairs in an individual. This deciphering or reading of the genome is what sequencing is all about. Costs of sequencing differ based on the methods employed to do the reading or the accuracy stressed upon in decoding the genome. Since an initial rough draft of the human genome was made available in 2000, the cost of generating a fairly accurate draft of any individual genome has fallen to a tenth, or to a ball park figure of around $1,000 (70,000 approximately). It has been known that the portion of the genes responsible for making proteins called the exome occupies about 1% of the actual gene. Rather than sequence the whole gene, many geneticists rely on exome maps (that is the order of exomes necessary to make proteins). However, it has been established that the non-exome portions also affect the functioning of the genes and that, ideally, to know which genes of a persons DNA are mutated the genome has to be mapped in its entirety. While India, led by the CSIR, first sequenced an Indian genome in 2009, it is only now that the organisations laboratories have been able to scale up whole-genome sequencing and offer them to the public.

Under IndiGen, the CSIR drafted about 1,000 youth from across India by organising camps in several colleges and educating attendees on genomics and the role of genes in disease. Some students and participants donated blood samples from where their DNA sequences were collected.

Globally, many countries have undertaken genome sequencing of a sample of their citizens to determine unique genetic traits, susceptibility (and resilience) to disease. This is the first time that such a large sample of Indians will be recruited for a detailed study. The project ties in with a much larger programme funded by the Department of Biotechnology to sequence at least 10,000 Indian genomes. The CSIRs IndiGen project, as it is called, selected the 1,000-odd from a pool of about 5,000 and sought to include representatives from every State and diverse ethnicities. Every person whose genomes are sequenced would be given a report. The participants would be informed if they carry gene variants that make them less responsive to certain classes of medicines. For instance, having a certain gene makes some people less responsive to clopidogrel, a key drug that prevents strokes and heart attack. The project involved the Hyderabad-based Centre for Cellular and Molecular Biology (CCMB), the CSIR-Institute of Genomics and Integrative Biology (IGIB), and cost 18 crore.

Anyone looking for a free mapping of their entire genome can sign up for IndiGen. Those who get their genes mapped will get a card and access to an app which will allow them and doctors to access information on whether they harbour gene variants that are reliably known to correlate with genomes with diseases. However, there is no guarantee of a slot, as the scientists involved in the exercise say there is already a backlog. The project is free in so far as the CSIR scientists have a certain amount of money at their disposal. The driving motive of the project is to understand the extent of genetic variation in Indians, and learn why some genes linked to certain diseases based on publications in international literature do not always translate into disease. Once such knowledge is established, the CSIR expects to tie up with several pathology laboratories who can offer commercial gene testing services.

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What is 'IndiGen' project that is sequencing Indian genes? - The Hindu

The National Institute of Health (NIH) has awarded the Willowbrook-based Institute for Basic Research (IBR) a $1.95 million grant over five years to support the study of rare diseases linked to genetic abnormalities.

Although the state-operated facility has expanded its mission in recent years, scientific research into developmental disabilities has been at the core of IBRs work since its founding more than five decades ago.

In that tradition, the NIH award will fund research led by Dr. Gholson Lyon, an IBR psychiatrist and scientist who heads the Genomic Medicine Laboratory in the Department of Human Genetics.

The grantprovides science investigators who have demonstrated ability to make major contributions to medical science the freedom to embark on ambitious, creative, and/or longer-term research projects, the New York State Office for People With Developmental Disabilities (OPWDD) said in a press release.

According to OPWDD, the research will further understanding of the genetic basis for rare diseases that include Ogden syndrome, which was discovered and named by Dr. Lyon.

Occurring in an estimated one of 1,000,000 births, Ogden syndrome is characterized by craniofacial abnormalities, hypotonia, global developmental delays, cryptorchidism, cardiac anomalies, and cardiac arrhythmias, says OPWDD.

The disease is connected to mutation of the NAA10 gene, which affects the bodys proteins and the ability of cells to proliferate. In addition to Ogden Syndrome, Dr. Lyons clinical studies will also focus on other diseases tied to NAA10, and a related gene, NAA15.

These diseases have a profound impact on families, said Dr. Lyon. I am grateful for this support from OPWDD and [the National Institute of Healths National Institute of General Medical Sciences].

Dr. Lyon also works with families at IBRs George A. Jervis Clinic, which offers diagnostic and consultative services for children and adults with intellectual and developmental disabilities.

In addition to Ogden syndrome and related diseases, Dr. Lyon also researches Fragile X syndrome, autism syndromes, and investigates the physiological basis of neuropsychiatric conditions, with the goal of expanding access to preventive services and treatment for those disorders, according to his online bio.

IBR Acting Director Joseph J. Maturi said, Dr. Lyons extensive medical and scientific training and experience will help him successfully undertake these ambitious and important studies."

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Willowbrook-based research facility receives $1.95 million grant to study rare diseases - SILive.com

Scientists have looked for immune system factors that might help mosquitoes ward off pathogens such as malarial parasites and indirectly protect humans from infection. Yale researchers found one by editing a single gene, which turns out to be crucial for female reproduction.

Researchers in the lab of Erol Fikrig, the Waldemar Von Zedtwitz Professor of Medicine (infectious diseases) and professor of epidemiology and of microbial pathogenesis, edited out a gene suspected of suppressing the mosquito immune system in females of the species Anopheles. They found that the reproductive systems of the mutant mosquitoes were severely disrupted and that the level of parasites that cause malaria was dramatically reduced, researchers report Oct. 28 in the Journal of Experimental Medicine.

When a mosquito does not have functional ovaries, the parasite that causes malaria will not survive well in the mosquito, Fikrig said. If we understand how malaria interacts with a mosquito, we can perhaps interfere with that process. However that is a long, long way off. This is not a new vaccine or treatment.

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Editing mosquito's gene wards off malaria and halts reproduction - Yale News

In September, Roivant Sciences, Vivek Ramaswamys umbrella biotech company, agreed to sell ownership of five of its Vant companies to Japans Sumitomo Dainippon Pharma for $3 billion. Sumitomo Dainippon also was buying an equity stake of more than 10% of Roivant shares.

The companies have released more details of the deal, which includes an option on six more Vant companies until 2024. The agreement was formally signed yesterday. Sumitomo will create an as-yet unnamed company to shift the five companies into. They will be run by Myrtle Potter, a former Genentech executive who has been the operating chair of Roivant since July 2018.

There is a $3 billion upfront fee. In addition, Sumitomo will offer a $350 million loan facility to Myovant to fund the launch of relugolix, its Phase III candidate for uterine fibroids if it is approved. The Japanese firm will also loan Urovant $200 million for its vibegron for overactive bladder.

If Sumitomo options the other six companies, will have acquired a pipeline of more than 25 clinical programs with multiple possible launches from 2020 to 2022. In addition to buying the five initial companies, the deal gives Sumitomo access to Roivants proprietary technology platforms, DrugOme and Digital Innovation. It will also enter separate strategic client relationships with Datavant and Alyvant.

The five Vant companies are Myovant Sciences, Urovant Sciences, Enzyvant Therapeutics, Altavant Sciences, and Spirovant Sciences. Spirovant is a new Vant that focuses on developing gene therapies for cystic fibrosis.

In addition to Potter, other Roivant team members will move to the new entity. They include Adele Gulfo, Roivants chief of Commercial Development, Sam Azoulay, Roivants chief medical officer, and Dan Rothman, Roivants chief information officer.

I am happy to announce that we have reached an agreement on the Strategic Alliance with Roivant, one of the strategic investments that we are making to address our challenges laid out in the Mid-Term Business Plan 2022, said Hiroshi Nomura, representative director, president and chief executive officer of Sumitomo Dainippon Pharma. This Strategic Alliance allows us to not only acquire potential blockbusters and innovative health technology platforms developed by Roivant, but it will also enable us to deepen our relationship with Roivant, a company that possesses an innovative business model and underlying culture. We expect this relationship will contribute significantly to the establishment of a position as a Global Specialized Player which we aspire to be in by 2033.

Spirovant is working to develop two therapies for cystic fibrosis. SPIRO-2101 uses an adeno-associated virus vector (AAV), like most gene therapies, to deliver a functional l CFTR gene to airway epithelial cells. SPIRO-2102 uses a proprietary lentiviral vector to deliver the gene. In animal models, both have showed restoration of CFTR function. The companys aerosolization technology is designed to maximize uptake in the lungs.

The two therapeutics leverage technology out of the University of Iowa Center for Gene Therapy at the Carver College of Medicine. Its collaboration with Childrens Hospital of Philadelphia (CHOP) was involved with the manufacture of the preclinical supply of the AAV products.

We are proud to enter this unique Alliance with Sumitomo Dainippon Pharma, said Ramaswamy. We hope that our contributions to this Alliance will enable Sumitomo Dainippon Pharma to realize its vision to be a global leader in the biopharmaceutical industry. In addition, we believe that this Alliance will increase the long-term value of each Vant in the Alliance through a combination of strong financial backing and other capabilities.

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The Roivant-Sumitomo Deal: $3 Billion, 5 Companies, $550 Million in Loans and an Option on 6 More Companies - BioSpace

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Veracyte, Inc. (Nasdaq: VCYT) today announced new data that advance understanding of the frequency, positive predictive value and co-occurrence of genomic alterations that are targeted by newly available and investigational precision medicine therapies for thyroid cancer. The findings were enabled by Afirma Xpression Atlas analyses, which uses RNA sequencing, of Veracytes extensive biorepository of thyroid nodule fine needle aspiration (FNA) samples from patients undergoing evaluation for thyroid cancer. The data were presented this week during the 89th Annual Meeting of the American Thyroid Association (ATA).

In one study, researchers assessed the frequency of ALK, BRAF, NTRK and RET fusions in nearly 48,000 consecutive patients whose thyroid nodule FNA samples were deemed indeterminate, suspicious for malignancy or malignant (Bethesda III/IV, V and VI categories, respectively) by cytopathology. The researchers found that 425 (0.89 percent) of the FNA samples harbored one of the alterations, with NTRK fusions the most common at 0.38 percent, followed by RET (0.32 percent), BRAF (0.13 percent) and ALK (0.06 percent). Additionally, RNA whole transcriptome sequencing demonstrated differences in the prevalence of these four fusions across Bethesda categories, with Bethesda V being the highest.

NTRK fusion inhibitors have received pan-cancer FDA approval and clinical trials have included selective inhibitors of ALK, BRAF, NTRK and RET, which makes their detection in patients with thyroid cancer of interest to physicians, said Mimi I. Hu, M.D., professor at The University of Texas MD Anderson Cancer Center, who presented the findings in a poster. As our understanding of the role of genomics in thyroid cancer advances, this information offers the potential to optimize initial treatment, predict response to treatment and prioritize selective targeted therapy should systemic treatment be needed.

In another study, researchers evaluated the positive predictive value of the NTRK, RET, BRAF and ALK fusions in 58 patients with indeterminate thyroid nodules (Bethesda III/IV categories) from Veracytes biorepository for whom surgical pathology diagnoses were available. They found that NTRK and RET fusions were associated with malignancy in 28 of 30 nodules, while risk of malignancy was lower among nodules with ALK (67 percent) or BRAF (75 percent). In a third study, researchers found that when using RNA sequencing data on a large sample of nearly 48,000 thyroid nodule FNA samples (Bethesda categories III-VI), they identified 263 co-occurrences of gene fusions and variants that were previously considered mutually exclusive.

The findings from these three studies underscore the power of our extensive biorepository of thyroid nodule FNA samples and our optimized RNA sequencing platform to advance understanding of the genomic underpinnings of thyroid cancer and to better capture the biology of thyroid lesions, said Richard T. Kloos, M.D., senior medical director, endocrinology, at Veracyte. As precision medicine therapies that target specific gene alterations emerge, understanding individual patients genomic profiles becomes increasingly important to physicians. Our Afirma Xpression Atlas provides this information at the same time as initial diagnosis with the Afirma Genomic Sequencing Classifier, or GSC, to help inform treatment decisions.

Also during the ATA meeting, Veracyte unveiled its new Afirma patient report, which in addition to identifying patients with benign or suspicious-for-cancer nodules among those deemed indeterminate by cytopathology, based on Afirma GSC results, now provides individualized and actionable variant and fusion information on each patient. This information includes: risk of malignancy, associated neoplasm type, relative risk of lymph node metastasis and extrathyroidal extension; availability of FDA-approved therapy; and genetic counseling and germline testing considerations. This information is also provided for patients with cytopathology results that are suspicious for malignancy or malignant (Bethesda V and VI).

About Afirma

The Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas provide physicians with a comprehensive solution for a complex landscape in thyroid nodule diagnosis. The Afirma GSC was developed with RNA whole-transcriptome sequencing and machine learning and helps identify patients with benign thyroid nodules among those with indeterminate cytopathology results in order to help patients avoid unnecessary diagnostic thyroid surgery. The Afirma Xpression Atlas provides physicians with genomic alteration content from the same fine needle aspiration samples that are used in Afirma GSC testing and may help physicians decide with greater confidence on the surgical or therapeutic pathway for their patients. The Afirma Xpression Atlas includes 761 DNA variants and 130 RNA fusion partners in over 500 genes that are associated with thyroid cancer.

About Veracyte

Veracyte (Nasdaq: VCYT) is a leading genomic diagnostics company that improves patient care by providing answers to clinical questions that inform diagnosis and treatment decisions without the need for costly, risky surgeries that are often unnecessary. The company's products uniquely combine RNA whole-transcriptome sequencing and machine learning to deliver results that give patients and physicians a clear path forward. Since its founding in 2008, Veracyte has commercialized seven genomic tests and is transforming the diagnosis of thyroid cancer, lung cancer and idiopathic pulmonary fibrosis. Veracyte is based in South San Francisco, California. For more information, please visit http://www.veracyte.com and follow the company on Twitter (@veracyte).

Cautionary Note Regarding Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "expect," "believe," "should," "may," "will" and similar references to future periods. Examples of forward-looking statements include, among others, the ability of Veracytes Afirma Xpression Atlas to analyze FNA samples to help diagnose thyroid cancer, the expected impacts of Veracytes collaboration with Johnson & Johnson in developing interventions for lung cancer, on Veracytes financial and operating results, on the timing of the commercialization of the Percepta classifier, and on the size of Veracytes addressable market. Forward-looking statements are neither historical facts nor assurances of future performance, but are based only on our current beliefs, expectations and assumptions. These statements involve risks and uncertainties, which could cause actual results to differ materially from our predictions, and include, but are not limited to: our ability to achieve milestones under the collaboration agreement with Johnson & Johnson; our ability to achieve and maintain Medicare coverage for our tests; the benefits of our tests and the applicability of clinical results to actual outcomes; the laws and regulations applicable to our business, including potential regulation by the Food and Drug Administration or other regulatory bodies; our ability to successfully achieve and maintain adoption of and reimbursement for our products; the amount by which use of our products are able to reduce invasive procedures and misdiagnosis, and reduce healthcare costs; the occurrence and outcomes of clinical studies; and other risks set forth in our filings with the Securities and Exchange Commission, including the risks set forth in our quarterly report on Form 10-Q for the quarter ended September 30, 2019. These forward-looking statements speak only as of the date hereof and Veracyte specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.

Veracyte, Afirma, Percepta, Envisia and the Veracyte logo are trademarks of Veracyte, Inc.

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Veracyte Announces New Data That Advance Understanding of Genomic Alterations Targeted by Precision Medicine Therapies for Thyroid Cancer - Business...

The mixture of bacteria shown in this photomicrograph contains five different species of the genus Bacteroides. (UW Medicine Photo / Mougous Lab / Kevin Cutler)

The balance of bacteria in your gut can make the difference between sickness and health and now scientists report that different species of bacteria share immunity genes to protect themselves against each others toxins and maintain their balance of power.

In effect, closely related species of bacteria acquire each others defense systems to fend off threats from alien invaders.

The findings appear in a paper published today in the journal Nature. The senior authors are Joseph Mougous, a microbiology professor at the University of Washington School of Medicine; and Elhanan Borenstein, a former UW Medicine geneticist who now works at Tel Aviv University.

The researchers focused on a particular species of gut bacteria known as Bacteroides fragilis, which produces toxic proteins to kill off other types of bacteria that get too close. They identified a cluster of genes that gives B. fragilis immunity to its own toxins but they also found the immunity factors in samples that didnt contain any B. fragilis bacterla.

This finding strongly suggests that these anti-B. fragilis immunity elements were encoded by other bacteria in the gut, the team reported in the Nature paper.

A statistical analysis led the researchers to suspect that the immunity genes were shared by at least four other Bacteroides species: B. ovatus, B. vulgatus, B. helcogenes and B. copracola. Gene sequencing confirmed their suspicion. The acquired shielding effect was observed in lab-dish conditions, as well as in the guts of living lab mice.

As a follow-up experiment, the researchers mixed one type of bacteria that had a specific group of immunity genes with another type that didnt have those genes. They found that the genes were transferred from the haves to the have-nots, giving them immunity as well.

Such transfers took place in other cases as well for example, when the target genes helped one species of Bacteroides fend off attacks by non-Bacteroides bacteria.

Gene-swapping thus appears to be a crucial element of a molecular arms race by which groups of bacteria maintain their status in the gut microbiome, the researchers said. So if scientists hope to treat diseases by tweaking the microbiome, they might have to account for that strategy in their medical playbook.

Two former UW postdoctoral researchers Benjamin Ross, whos now on Dartmouth Colleges faculty; and Adrian Verster, a bioinformatician at Health Canada are the principal authors.of the Nature paper, titled Human Gut Bacteria Contain Acquired Interbacterial Defence Systems. In addition to Mougous and Borenstein, the other study authors include Matthew Radey, Danica Schmidtke, Christopher Pope, Lucas Hoffman, Adeline Hajjar and S. Brook Peterson.

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Scientists track the arms race thats playing out between bacteria in your gut - GeekWire

Comparison is the essential valuation activity

Readers familiar with our work may want to skip to the "Comparing Details" section below.

Advances in Genome understanding and prospective adjustments continue at a startling pace. Equity investments provide a means of maintaining perspective and other SA contributors help with the industry development details.

This article rewards investors who choose to direct their investments of TIME and capital to those alternatives with the highest likelihood of successful rates of return among ones compared under identical important measures.

Now, Editas Medicine (EDIT) provides attractive answers to these questions:

These are questions often neither asked nor answered by many investment analysis reports. The commonplace approach is to present those aspects of one investment which may set it apart from others, but fail to make the essential decision-supporting step of comparing alternatives on an equal-measure basis.

Instead of limiting a value-search to industry competitors, our focus is on the alternatives which may address the investor's objectives of his investing mission, not necessarily of a stock candidate's competitive industry concerns.

To that end we turn to an information expert on what is currently of importance to investors - YAHOO Finance - and what also diverts the attention of investors initially interested in the stock of Editas Medicine. From its website traffic records Yahoo lists five other stocks "People also watch." They are NTLA, SGMO, BLUE, ONCE, and CLLS.

With the alternative investment choices in hand, we then turn to folks involved every market day with making bets (usually big bets) about how far their prices are likely to get pushed - both up and down. Those price limits are defined in the choices they make in the way they will protect their capital which must be exposed to market risk as they conduct their every-day market-making activities in large-volume "block trade" transactions.

Price range forecasts are being made in separate hedging deals over time periods defined by the contract lives of the derivative securities involved. Those judgments contain the updated "fundamentals" of interest to all evaluators, collected 24x7 by armies of market-maker (MM) employees world-wide.

Such forecasts are constantly being refined every moment investment markets are operating, and are made part of every market-day's closing records. They provide an historical record (in subsequent market price actions) of how well the "smart money" can make useful forecasts - for specific stocks, ETFs, and indexes.

Present-day markets are driven by major investing organizations commanding multi-billion dollar portfolios with stock contents which can only be adjusted by negotiated volume (block) trades between peers, not by "open auction". Such trades set and move posted prices.

The individual investor typically is merely along for the ride. He/she needs to have a sense of where the negotiators are likely to head, pricewise. Conventional analysis often provides superficial descriptions and little linkage between operating minutia and price forecasts. As an example here is how Yahoo Finance reports on EDIT.

Editas Medicine, Inc. operates as a clinical stage genome editing company. The company focuses on developing transformative genomic medicines to treat a range of serious diseases. It develops a proprietary genome editing platform based on CRISPR technology to target genetically addressable diseases and therapeutic areas. The company develops EDIT-101 for Leber Congenital Amaurosis type 10, a genetic form of vision loss that leads to blindness in childhood. It also develops other therapies for eye diseases, such as Usher Syndrome 2A, which is a form of retinitis pigmentosa that also includes hearing loss; Retinitis Pigmentosa, a progressive form of retinal degeneration; and Herpes Simplex Virus 1 that causes lifelong infections leading to ocular and oral disease.

In addition, the company develops hematopoietic stem cells for treating sickle cell disease and beta thalassemia. It has a research collaboration with Juno Therapeutics, Inc. to develop engineered T cells for cancer; strategic alliance and option agreement with Allergan Pharmaceuticals International Limited to discover, develop, and commercialize new gene editing medicines for a range of ocular disorders; and strategic research collaboration and cross-licensing agreement with BlueRock Therapeutics to combine their respective genome editing and cell therapy technologies to discover, develop, and manufacture engineered cell medicines. The company also has a strategic research collaboration agreement with Editas Medicine, Inc. to explore in vivo delivery of genome editing medicines to treat neurological diseases. The company was formerly known as Gengine, Inc. and changed its name to Editas Medicine, Inc. in November 2013. Editas Medicine, Inc. was founded in 2013 and is headquartered in Cambridge, Massachusetts.

Not much help, is it?

Instead, here is what the MMs' hedging actions tell today about how high (and low) the stocks might get priced, and how they each behaved subsequent to prior forecasts like the ones now being seen:

Figure 1

The essence of valuation is in comparison, which requires that the compared measures be as close to identical as possible. To that end we place all of our valuations in a carefully defined set of measures, and describe them in as parallel set of comparisons as is possible.

To do so often presents what many readers recognize as text and ideas they have encountered before, as they have in our just-published comparison between Microsoft and Boeing. The use of the heading for this section of the article as an accelerant to reading provides for experienced readers an economy of time and effort, while leaving for the newly-initiated the opportunity for an important introduction.

What is important to us in this analysis is how big a price gain is in prospect, column [E], and how likely is today's RI forecast to produce a profit [H] as a proportion of the [L] sample of such forecasts. That combination result appears in the [I] %payoff which includes loser forecasts as well as the 82% winners. The size of [I] relative to [E] is a measure of [E]'s credibility in [N].

Time required [J] to accomplish the payoff is another important dimension for any investment mission. The retirement, tuition, or health emergency clock won't patiently wait for "long-term-trend" investments to be "sure" (like EK, GM, GE, and others) of their "passive investment" buy&hold strategy results. Compound Annual Gain Rates (CAGR) are the essential measures [K]. Figure 3's rows are ranked by the historical results (of today's RI) statistic.

One additional complication of being time-efficient in an investment strategy is that the score-keeping can't be easily sliced up into uniform time periods. That is not what happens to holdings in an active investment strategy. Gains (and losses) occur in irregular lumps of time, and we need to evaluate likely prospects in the way they may be accumulated.

What is done in proper financial analysis of any capital commitment is to anticipate the RATE of gain or cost in units of change per time of involvement. The most commonly used measure is basis points per day, where a basis point is 1/100th of a percent.

That's a tiny unit, but is what works best. Put together and maintained each day for a year, 19 of them would double your investment. They can be powerful.

In Figure 1 we use the Odds of gain [H] as a weight for the average prior payoffs [I], and take the complement of [H] ( 100 - H ) as a weight for the risk prospect [F]. Put together as [O] + [P] in [Q] we have an odds-weighted net outcome of each row's prior MM RI forecast sample [L]. Then by converting those [Q] nets into bp/day in [R] we have a guide to making investment selection decisions across a broader array of alternatives.

Taking measurements into such precision where the potentials are great for errors in forecasting may only serve to point out the limits of their usefulness. And where the differences between alternatives are great, the efforts involved may not be practical. But the fact remains that investors and investment organizations are determined to risk capital in these uncertain ventures, and progress in some areas of the unknown need guide-rails.

So figure 1 may tell us that if the future is repeated then in this case EDIT is a superior portfolio choice to any of the five alternatives generally being considered by investors consulting Yahoo Finance's data. EDIT's stock superiority lies principally in that in the next 3 months it has better odds of seeing a price +19% higher while encountering interim price drawdowns not significantly worse than any of the alternative stock investments, and do it in approximately the next 8 weeks.

That rate of gain is a CAGR of +201%, which compares to a probable parallel investment in the S&P 500 index ETF (SPY) of some +15%. Out of a population of over 2,700 other coming price range forecasts from the same source an average CAGR of +17% involves roughly equal interim risk exposure of -10% which is typically not only encountered, but also suffered in terms of actual capital loss experience, reducing that forecast population's expected +14% gain to only +3% in the process.

Meanwhile, the best 20 candidate stock investments from that population actually achieved +19% gains, better than the +14% expected, and by being alert to day-by-day price moves accomplished them in the same 8 week average holding period of EDIT, for CAGR rewards at a 342% rate.

Will all these price changes be repeated? Probably not precisely, but at least you have some norms to compare with.

To provide a sense of how EDIT price range forecasts by MMs have been trending recently Figure 2 shows daily expectations for the past 6 months and Figure 3 shows once-a-week excerpts over the past two years.

Figure 2

The small blue picture here shows the distribution of forecast Range Indexes during the past 5 years' 1261 market days. Recording the daily balance between expected upside and downside price changes likely, the current measure of 29 is clearly below its visual average, supporting the 82/100 odds of higher coming prices.

Figure 3

Editas Medicine presents evidences of coming price change prospects which are superior to many relevant equity investment alternatives, and justify its buy as a near-term wealth-building investment.

Disclosure: I/we have no positions in any stocks mentioned, but may initiate a long position in EDIT over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Peter Way and generations of the Way Family are long-term providers of perspective information, earlier helping professional investors and now individual investors, discriminate between wealth-building opportunities in individual stocks and ETFs. We do not manage money for others outside of the family but do provide pro bono consulting for a limited number of not-for-profit organizations.

We firmly believe investors need to maintain skin in their game by actively initiating commitment choices of capital and time investments in their personal portfolios. So, our information presents for D-I-Y investor guidance what the arguably best-informed professional investors are thinking. Their insights, revealed through their own self-protective hedging actions, tell what they believe is most likely to happen to the prices of specific issues in coming weeks and months. Evidences of how such prior forecasts have worked out are routinely provided in the SA blog of my name.

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Editas Medicine In The Realm Of Designer Humans - Seeking Alpha

A new triple-drug therapy that tackles the genetic causes of cystic fibrosis has been shown to be highly effective in treating the rare life-threatening disorder, scientists reportedfollowing landmark clinical trials.

The finding, 30 years after the gene that causes the disease was identified, was called a "cause for celebration" by Francis Collins, the director of the National Institutes of Health who was part of the team that made the original genetic discovery.

Trikafta is a combination of three drugs that target the CFTR gene responsible for the disease, which affects over 1,000 people in Ireland.

The gene results in the formation of thick mucus build-up in the lungs, digestive tract and other parts of the body.

That in turn results in respiratory and digestive problems, and exposes patients to complications such as infections and diabetes.

Average life expectancy is in the 30s and 40s and was historically even lower before advances in drugs that alleviate symptoms.

The new therapy targets the most common mutation of the CFTR gene, the Phe508del mutation, which represents around 90%of cases.

"The results of a pair of phase 3 clinical trials in the Journal and in a simultaneous publication in the Lancet document impressive benefits," Mr Collins wrote in an editorial for the New England Journal of Medicine.

The two trials examined how much air patients could expel in a forced breath, an established marker of the disease's progression.

In the first trial, mean levels increased by 13.8%compared to a placebo, while in the second trial, mean levels rose 10% from baseline compared to an earlier drug combination.

"This should be a cause for major celebration," said Mr Collins, but he added that more work was needed on patients with other forms of mutations who would not respond to the new therapy.

Beyond that, he added, the best outcome would come when the more than 70,000 people with the disease worldwide do not need drugs because of a permanent cure achieved through gene editing.

The rest is here:
New therapy to tackle cystic fibrosis highly effective - RTE.ie

SINGAPORE - The Rare Disease Fund (RDF) now covers Singaporeans with Pompe disease - a rare inherited neuromuscular disorder where patients can incur medical expenses in excess of $500,000 each year.

The committee overseeing the fund announced on Sunday (Nov 3) that citizens can now apply for financial aid to help with their medical expenses for the disease which affects about one in every 40,000 live births.

With the addition, the fund now covers four conditions including primary bile acid synthesis disorder; Gaucher disease; and hyperphenylalaninaemia due to tetrahydrobiopterin (BH4) deficiency.

The fund has approved two applications for financial support so far. One of the beneficiaries is Mr Geoffrey Toi, a public servant whose three-year-old son Christopher suffers from primary bile acid synthesis disorder.

The condition interferes with the production of bile acids and if untreated, can lead to liver failure.

The fund covers a larger portion of Christopher's medication costs, which is currently about $6,250 a month, as compared to Medifund Junior, which had previously subsidised part of his medical fees.

"It was a blessing when this fund was announced, because it specifically covered his condition. Every bit of help matters," said Mr Toi, 35.

The fund was launched by the Ministry of Health (MOH) and SingHealth Fund in July this year. It combines community donations and Government-matched contributions to provide aid for Singapore citizens with specific rare diseases.

Senior Minister of State for Health and Law Edwin Tong said on Sunday that the fund recently received significant support from Temasek and the Tsao Family Fund.

"The listing of Pompe is possible because we have so many generous benefactors who have stepped forward selflessly, with a lot of compassion, to donate to the RDF," he added.

The fund has grown from $70 million last July to about $90 million, with the government matching community donations by three to one.

In addition, the Government is funding all operational expenses involved in managing the fund, ensuring that all donations received will be used solely for supporting patients.

"We hope that philanthropists, companies, community groups and individuals will continue to come forward as a society, as a community to help support patients with rare diseases... As more funds are raised, the Rare Disease Fund can be expanded further to cover even more types of treatments and more patients in future," said Mr Tong, who was attending a community carnival organised by Mount Alvernia Hospital in support of the RDF.

The carnival in Punggol raised more than $200,000 for beneficiaries of the fund. The sum includes three-to-one government matching.

Rare diseases are defined by MOH as conditions that affect fewer than one in 2,000 people, and mostly are genetic and often surface during childhood. There are no official numbers on how many people in Singapore have such rare diseases.

In some cases, effective treatments are available and the medicines can substantially increase patients' life expectancies and improve quality of life.

However, MOH noted that these medicines can be very costly, going up to hundreds of thousands of dollars a year, and patients will often need to take them for the rest of their lives.

Pompe disease is caused by a defective gene that results in a deficiency of an enzyme.

It results in the excessive build-up of a substance called glycogen, a form of sugar that is stored in a specialised compartment of muscle cells throughout the body.

Symptoms of the disease include extreme muscle weakness and breathing difficulties. The progressive nature of the disease means that it worsens over time, with the speed of progression varying from patient to patient.

Mr Kenneth Mah, whose 10-year-old daughter Chloe has Pompe disease, cheered the move to cover the disease under the RDF.

While insurance covers much of her treatment cost now - which is in excess of $40,000 a month - it may not be enough in future as she gets older and needs more of medicine.

"It gives us a greater peace of mind," said Mr Mah, 49, who ended his mobile phone business to become the main caregiver for Chloe.

Mr Mah is also the co-founder of the Rare Disorders Society Singapore.

"We hope that the fund will be able to cover all rare disorders in the future, as it gets more support from society."

More information on the RDF is available at http://www.kkh.com.sg/rarediseasefund

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Rare Disease Fund now covers Pompe disease, a rare inherited neuromuscular disorder - The Straits Times